Somatic TEK variant with intraarticular venous malformation and knee hemarthrosis treated with rapamycin

Salma Adham (1, 2) , Nicole Revencu (3) , Sandrine Mestre (1, 2) , Monira Nou‐howaldt (1) , Hélène Vernhet‐kovacsik (4, 5) , Isabelle Quéré (1, 2)

1 CHRU Montpellier - Hôpital Saint Eloi
2 IDESP - Institut Desbrest de santé publique
3 Cliniques Universitaires Saint-Luc [Bruxelles]
4 Hôpital Arnaud de Villeneuve [CHRU Montpellier]
5 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]

Background: Venous malformations (VMs) are the most common vascular anomalies and have been associated with somatic variants in TEK. Current treatment of VM joint component might be challenging due to the size or location of some lesions or ineffective with recurrence of malformed veins. Targeted molecular therapies after identification of genetic defects might be an alternative. Methods: We report a case with intraarticular bleeding due to VM with a TEK pathogenic somatic variant treated with rapamycin. Results: A 26-year-old female patient was evaluated for right calf pain secondary to venous malformation of the right inferior limb with an intraarticular component in the right knee. Hemarthrosis and degenerative chondropathy of the knee were evidenced at MRA. Molecular diagnosis evidenced a pathogenic somatic TEK variant. Rapamycin was introduced to stop bleeding, with good tolerance and efficacy. Conclusion: The TEK receptor signals through the PI3K/AKT/mTOR pathway and TEK mutations have been linked to AKT activation. As rapamycin acts against angiogenesis and reduces phosphorylated-AKT levels, targeted molecular therapy should be discussed as first-line therapy in patients with proven molecular diagnosis and diffuse VM inaccessible to conventional treatment.

Mots clés: TEK/TIE2; Genetics; Rapamycin; Vascular malformation; Venous malformation

Domaines: Génétique humaine; Médicaments

Salma Adham, Nicole Revencu, Sandrine Mestre, Monira Nou‐howaldt, Hélène Vernhet‐kovacsik, et al.. Somatic TEK variant with intraarticular venous malformation and knee hemarthrosis treated with rapamycin. Molecular Genetics & Genomic Medicine, In press, ⟨10.1002/mgg3.1931⟩. ⟨hal-03671182⟩